BACKGROUND: Risks of coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) may be different in the presence of peripheral vascular disease (PVD). METHODS AND RESULTS: We analyzed outcomes of 550 patients with PVD enrolled in the Bypass Angioplasty Revascularization Investigation randomized trial and registry. Compared with 1770 patients without PVD, those with PVD were older and had a greater prevalence of medical comorbid conditions. No significant differences in coronary anatomy or PTCA success rates were found. The risk of any major complication (death, myocardial infarction, stroke, coma, or emergency revascularization) after PTCA was significantly higher among patients with PVD (11.7% versus 7.8%, P=0.027). In multivariate analysis, this represented a 50% increase in the odds of having any major complication (multivariate odds ratio, 1.5; P=0. 032). Among patients undergoing CABG, the risk of major complications was found to be markedly higher for patients with PVD (12%) than those without (6.1%, P=0.003) even after controlling for baseline differences (multivariate odds ratio, 1.8; P=0.018). Major differences between the PTCA and CABG groups were related primarily to a higher risk of neurological complications in PVD patients who had CABG (multivariate odds ratio, 2.8; P<0.001). CONCLUSIONS: We conclude that patients with PVD are at high risk for periprocedural complications after myocardial revascularization, in particular neurological events.